DESCRIPTION: The proposed research is a treatment-matching study to test whether adding fluoxetine pharmacotherapy to behavioral cessation treatment improves the depression-prone smoker's ability to quit. The investigators will randomize 144 smokers with a prior history of depression and 206 smokers who lack such a history to a double-blind treatment with either 60 mg fluoxetine or placebo, while they undergo cognitive behavioral treatment to quit smoking. The main study outcome is biologically verified abstinence 6 months after treatment. The administration of placebo and fluoxetine would begin 3 weeks before the quit smoke date and will continue for 2 months post-quit date (totaling 11 weeks on drug/placebo). Cognitive behavioral treatment will be weekly before quitting and biweekly after quitting. There will be monthly follow-up evaluations for six months after the quit date. The research tests both the Selective Benefit Hypothesis and the Generalized Benefit Hypothesis of fluoxetine's effects is theoretically and clinically important. The mechanism of action is that the drug diminishes compulsive smoking behavior, obsessional cigarette craving, and nicotine withdrawal dysphoria that occur independently of depressive vulnerability. The significance of this research is that it evaluates a humane, potentially cost-effective treatment for nicotine dependence in depression-prone smokers, and may advance understanding of shared predisposing factors that generate this comorbidity.